Study Identifies Potential Predictor of Clinical Outcome in Patients With Lung Cancer Treated With the Investigational Immunotherapy MK-3475

SAN DIEGO — Among patients with non-small cell lung cancer (NSCLC) treated with the investigational immune checkpoint inhibitor MK-3475, those whose tumors had high levels of the protein PD-L1 had significantly better outcomes, according to results of a phase I clinical trial presented here at the AACR Annual Meeting 2014, April 5-9.


Preliminary data from the trial, which were reported earlier this year, showed that MK-3475 treatment was well tolerated and led to durable, objective responses in previously treated patients with NSCLC, particularly those with tumors found to have high levels of PD-L1 prior to treatment.

The latest results extend these data, showing that at six months after starting treatment, 41 percent of patients whose tumors had high levels of PD-L1 had no disease progression, compared with 17 percent of those whose tumors had low levels of PD-L1. Similarly, 72 percent of patients whose tumors had high levels of PD-L1 were alive at this time, compared with 53 percent of those whose tumors had low levels of PD-L1.

“Patients with previously treated NSCLC have a very poor outlook and there is a real need for new treatment options,” said Leena Gandhi, M.D., Ph.D., assistant professor of medicine at Harvard Medical School in Boston. “The responses we have seen among patients whose tumors express high levels of PD-L1 appear to be quite durable, which is extremely exciting.

“Immune cells called T cells are naturally capable of destroying cancer cells,” explained Gandhi, who is also a thoracic oncologist at the Dana-Farber Cancer Institute. “But some cancer cells are able to prevent T cells from attacking them by activating the T cells’ ‘brakes.’ One way they do this is via a protein called PD-L1 on their surface, which attaches to a protein on the surface of T cells, PD-1. MK-3475 disables this brake by blocking PD-1 on the T cells and preventing it from attaching to PD-L1.”

Gandhi and colleagues enrolled patients with NSCLC to multiple cohorts on the phase I clinical trial. When they analyzed the data based on pretreatment tumor PD-L1 levels, information they were able to obtain for 146 patients, it was found that levels of PD-L1 of greater than 50 percent, as measured by immunohistochemistry, served as the best cutoff point for differentiating outcomes for PD-L1-positive versus PD-L1-negative tumors. For the group of 41 patients with high pretreatment tumor PD-L1 levels, response rate was 37 percent as compared with 11 percent for those with low pretreatment tumor PD-L1 levels.

“These data strongly suggest that high levels of tumor PD-L1 may be a good biomarker for determining which patients with NSCLC are most likely to benefit from treatment with MK-3475,” said Gandhi. “We will present outcome data on this full group of patients who have now had PD-L1 expression analyzed. These results extend our findings from the initial 38 patients, and an ongoing, randomized study will prospectively evaluate the role of PD-L1 expression in determining outcome to MK3475 versus docetaxel therapy.”

This study was funded by Merck. Gandhi declares no conflicts of interest.

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